Variable impact of tizanidine on the medium latency reflex of upper and lower limbs

Abstract

Sudden limb displacement evokes a complex sequence of compensatory muscle activity. Following the short-latency reflex and preceding voluntary reactions is an epoch termed the medium-latency reflex (MLR) that could reflect spinal processing of group II muscle afferents. One way to test this possibility is oral ingestion of tizanidine, an alpha-2 adrenergic agonist that inhibits the interneurons transmitting group II signals onto spinal motor neurons. We examined whether group II afferents contribute to MLR activity throughout the major muscles that span the elbow and shoulder. MLRs of ankle muscles were also tested during walking on the same day, in the same participants as well as during sitting in a different group of subjects. In contrast to previous reports, the ingestion of tizanidine had minimal impact on MLRs of arm or leg muscles during motor actions. A significant decrease in magnitude was observed for 2/16 contrasts in arm muscles and 0/4 contrasts in leg muscles. This discrepancy with previous studies could indicate that tizanidine's efficacy is altered by subtle changes in protocol or that group II afferents do not substantially contribute to MLRs.

http://ift.tt/2CuWMA1

The Effect of Muscle Direction on the Predictions of Finite Element Model of Human Lumbar Spine

The normal physiological loads from muscles experienced by the spine are largely unknown due to a lack of data. The aim of this study is to investigate the effects of varying muscle directions on the outcomes predicted from finite element models of human lumbar spine. A nonlinear finite element model of L3–L5 was employed. The force of the erector spinae muscle, the force of the rectus abdominis muscle, follower loads, and upper body weight were applied. The model was fixed in a neural standing position and the direction of the force of the erector spinae muscle and rectus abdominis muscle was varied in three directions. The intradiscal pressure, reaction moments, and intervertebral rotations were calculated. The intradiscal pressure of L4-L5 was 0.56–0.57 MPa, which agrees with the in vivo pressure of 0.5 MPa from the literatures. The models with the erector spinae muscle loaded in anterior-oblique direction showed the smallest reaction moments (less than 0.6 Nm) and intervertebral rotations of L3-L4 and L4-L5 (less than 0.2 degrees). In comparison with loading in the vertical direction and posterior-oblique direction, the erector spinae muscle loaded in the anterior-oblique direction required lower external force or moment to keep the lumbar spine in the neutral position.

http://ift.tt/2EHPNSj

20-year risk of breast cancer recurrence

http://ift.tt/2DXQHZZ

Oncogenic N-Ras Stimulates SRF-Mediated Transactivation via H3 Acetylation at Lysine 9

Signal transduction pathways regulate the gene expression by altering chromatin dynamics in response to mitogens. Ras proteins are key regulators linking extracellular stimuli to a diverse range of biological responses associated with gene regulation. In mammals, the three ras genes encode four Ras protein isoforms: H-Ras, K-Ras4A, K-Ras4B, and N-Ras. Although emerging evidence suggests that Ras isoforms differentially regulate gene expressions and are functionally nonredundant, the mechanisms underlying Ras specificity and Ras signaling effects on gene expression remain unclear. Here, we show that oncogenic N-Ras acts as the most potent regulator of SRF-, NF-κB-, and AP-1-dependent transcription. N-Ras-RGL2 axis is a distinct signaling pathway for SRF target gene expression such as Egr1 and JunB, as RGL2 Ras binding domain (RBD) significantly impaired oncogenic N-Ras-induced SRE activation. By monitoring the effect of Ras isoforms upon the change of global histone modifications in oncogenic Ras-overexpressed cells, we discovered that oncogenic N-Ras elevates H3K9ac/H3K23ac levels globally in the chromatin context. Importantly, chromatin immunoprecipitation (ChIP) assays revealed that H3K9ac is significantly enriched at the promoter and coding regions of Egr1 and JunB. Collectively, our findings define an undocumented role of N-Ras in modulating of H3 acetylation and in gene regulation.

http://ift.tt/2DVNTwf

Eryptosis: An Erythrocyte’s Suicidal Type of Cell Death

Erythrocytes play an important role in oxygen and carbon dioxide transport. Although erythrocytes possess no nucleus or mitochondria, they fulfil several metabolic activities namely, the Embden-Meyerhof pathway, as well as the hexose monophosphate shunt. Metabolic processes within the erythrocyte contribute to the morphology/shape of the cell and important constituents are being kept in an active, reduced form. Erythrocytes undergo a form of suicidal cell death called eryptosis. Eryptosis results from a wide variety of contributors including hyperosmolarity, oxidative stress, and exposure to xenobiotics. Eryptosis occurs before the erythrocyte has had a chance to be naturally removed from the circulation after its 120-day lifespan and is characterised by the presence of membrane blebbing, cell shrinkage, and phosphatidylserine exposure that correspond to nucleated cell apoptotic characteristics. After eryptosis is triggered there is an increase in cytosolic calcium (Ca2+) ion levels. This increase causes activation of Ca2+-sensitive potassium (K+) channels which leads to a decrease in intracellular potassium chloride (KCl) and shrinkage of the erythrocyte. Ceramide, produced by sphingomyelinase from the cell membrane's sphingomyelin, contributes to the occurrence of eryptosis. Eryptosis ensures healthy erythrocyte quantity in circulation whereas excessive eryptosis may set an environment for the clinical presence of pathophysiological conditions including anaemia.

http://ift.tt/2lKZlTS

Cancers, Vol. 10, Pages 8: Modification of Epigenetic Histone Acetylation in Hepatocellular Carcinoma

Cancers, Vol. 10, Pages 8: Modification of Epigenetic Histone Acetylation in Hepatocellular Carcinoma

Cancers doi: 10.3390/cancers10010008

Authors: Kwei-Yan Liu Li-Ting Wang Shih-Hsien Hsu

Cells respond to various environmental factors such as nutrients, food intake, and drugs or toxins by undergoing dynamic epigenetic changes. An imbalance in dynamic epigenetic changes is one of the major causes of disease, oncogenic activities, and immunosuppressive effects. The aryl hydrocarbon receptor (AHR) is a unique cellular chemical sensor present in most organs, and its dysregulation has been demonstrated in multiple stages of tumor progression in humans and experimental models; however, the effects of the pathogenic mechanisms of AHR on epigenetic regulation remain unclear. Apart from proto-oncogene activation, epigenetic repressions of tumor suppressor genes are involved in tumor initiation, procession, and metastasis. Reverse epigenetic repression of the tumor suppressor genes by epigenetic enzyme activity inhibition and epigenetic enzyme level manipulation is a potential path for tumor therapy. Current evidence and our recent work on deacetylation of histones on tumor-suppressive genes suggest that histone deacetylase (HDAC) is involved in tumor formation and progression, and treating hepatocellular carcinoma with HDAC inhibitors can, at least partially, repress tumor proliferation and transformation by recusing the expression of tumor-suppressive genes such as TP53 and RB1.

http://ift.tt/2EGi6Rh

Prevalence of Musculoskeletal Disorders Among Surgeons Performing Minimally Invasive Surgery: A Systematic Review

Objective: The aim of this study was to review musculoskeletal disorder (MSD) prevalence among surgeons performing minimally invasive surgery. Background: Advancements in laparoscopic surgery have primarily focused on enhancing patient benefits. However, compared with open surgery, laparoscopic surgery imposes greater ergonomic constraints on surgeons. Recent reports indicate a 73% to 88% prevalence of physical complaints among laparoscopic surgeons, which is greater than in the general working population, supporting the need to address the surgeons' physical health. Methods: To summarize the prevalence of MSDs among surgeons performing laparoscopic surgery, we performed a systematic review of studies addressing physical ergonomics as a determinant, and reporting MSD prevalence. On April 15 2016, we searched Pubmed, EMBASE, the Cochrane Library, Web of Science, CINAHL, and PsychINFO. Meta-analyses were performed using the Hartung-Knapp-Sidik-Jonkman method. Results: We identified 35 articles, including 7112 respondents. The weighted average prevalence of complaints was 74% [95% confidence interval (95% CI) 65–83]. We found high inconsistency across study results (I2 = 98.3%) and the overall response rate was low. If all nonresponders were without complaints, the prevalence would be 22% (95% CI 16–30). Conclusions: From the available literature, we found a 74% prevalence of physical complaints among laparoscopic surgeons. However, the low response rates and the high inconsistency across studies leave some uncertainty, suggesting an actual prevalence of between 22% and 74%. Fatigue and MSDs impact psychomotor performance; therefore, these results warrant further investigation. Continuous changes are enacted to increase patient safety and surgical care quality, and should also include efforts to improve surgeons' well-being.

http://ift.tt/2ild0Au